A correlation of endocrine and anticancer effects of some antagonists of GHRH

Magdolna Kovács, Andrew V Schally, Florian Hohla, Ferenc G. Rick, Éva Pozsgai, Luca Szalontay, József L. Varga, Márta Zarándi

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

GHRH receptor antagonists inhibit growth and metastasis of a large number of experimental tumors expressing the pituitary GHRH receptor (pGHRH-R) and its major splice variant SV1. In this study, using Western blot, we demonstrated that DBTRG-05 and U-87MG human glioblastoma cell lines express pGHRH-R at levels 6-15 times higher than SV1. To reveal a correlation between the anticancer activity and the endocrine potency on inhibition of GH release, we compared the antitumor effect of GHRH antagonists JV-1-63 and MZJ-7-138 on growth of DBTRG-05 human glioblastomas grafted into athymic nude mice with their inhibitory potency on GH release. JV-1-63 strongly suppressed the stimulated GH secretion induced by clonidine in rats and inhibited the exogenous GHRH-induced GH surge by 88-99% in vivo and in vitro. MZJ-7-138 decreased the stimulated GH secretion by 58% in vitro and showed only a tendency to inhibit GH secretion in vivo. The strong inhibitor of GH release JV-1-63 reduced tumor growth of DBTRG-05 glioblastomas in nude mice by 46%, while the weak GH release suppressor MZJ-7-138 did not have an effect. Exposure of DBTRG-05 cells to the GHRH antagonists in vitro caused an upregulation of mRNA expression for pGHRH-R and a downregulation of SV1 expression, with JV-1-63 having significantly greater effects than MZJ-7-138. Our results demonstrate that a positive correlation exists between the endocrine potency and the antiproliferative efficacy of GHRH antagonists in tumors strongly expressing pGHRH-R.

Original languageEnglish
Pages (from-to)1839-1846
Number of pages8
JournalPeptides
Volume31
Issue number10
DOIs
StatePublished - Oct 1 2010

Fingerprint

Glioblastoma
Nude Mice
Tumors
Growth
Clonidine
Pituitary Neoplasms
Rats
Neoplasms
Up-Regulation
Down-Regulation
Western Blotting
Cells
Neoplasm Metastasis
Cell Line
Messenger RNA
somatotropin releasing hormone receptor
In Vitro Techniques

Keywords

  • Anticancer
  • GH
  • GHRH antagonist
  • GHRH receptor
  • Glioblastoma
  • mRNA

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

Cite this

Kovács, M., Schally, A. V., Hohla, F., Rick, F. G., Pozsgai, É., Szalontay, L., ... Zarándi, M. (2010). A correlation of endocrine and anticancer effects of some antagonists of GHRH. Peptides, 31(10), 1839-1846. https://doi.org/10.1016/j.peptides.2010.07.006

A correlation of endocrine and anticancer effects of some antagonists of GHRH. / Kovács, Magdolna; Schally, Andrew V; Hohla, Florian; Rick, Ferenc G.; Pozsgai, Éva; Szalontay, Luca; Varga, József L.; Zarándi, Márta.

In: Peptides, Vol. 31, No. 10, 01.10.2010, p. 1839-1846.

Research output: Contribution to journalArticle

Kovács, M, Schally, AV, Hohla, F, Rick, FG, Pozsgai, É, Szalontay, L, Varga, JL & Zarándi, M 2010, 'A correlation of endocrine and anticancer effects of some antagonists of GHRH', Peptides, vol. 31, no. 10, pp. 1839-1846. https://doi.org/10.1016/j.peptides.2010.07.006
Kovács, Magdolna ; Schally, Andrew V ; Hohla, Florian ; Rick, Ferenc G. ; Pozsgai, Éva ; Szalontay, Luca ; Varga, József L. ; Zarándi, Márta. / A correlation of endocrine and anticancer effects of some antagonists of GHRH. In: Peptides. 2010 ; Vol. 31, No. 10. pp. 1839-1846.
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